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rTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway

Molecular Neurobiology volume 55, pages 3946–3958 (2018)Cite this article

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Currently, using the single prolonged stress (SPS) rat model for PTSD, we investigated the glutamatergic transmission and neural plasticity changes in the anterior cingulate cortex (ACC) after SPS induction and explored the protective effects and mechanism of rTMS treatment. We found that high-frequency rTMS (HrTMS, 15 Hz) treatment significantly relieved the impaired glutamatergic receptors in the ACC after SPS treatment by significantly increasing NMDAR and AMPAR expression. Simultaneously, HrTMS blocked inhibited neuronal phosphatase and tensin homologue on chromosome 10 (PTEN)/Akt signalling in the ACC after SPS treatment by decreasing PTEN expression and increasing Akt phosphorylation, which is critically involved in the regulation of memory and synaptic plasticity. The PTEN inhibitors bpV and small interfering RNA and the Akt inhibitor wortmannin were stereotaxically administered to the ACC after SPS treatment to advance the mechanistic study. Analysis by Western blot, double immunofluorescence, Golgi staining and behavioural tests demonstrated that the effects of rTMS on PTEN/Akt activation, glutamatergic receptor expression, neuronal synaptic plasticity and PTSD-related behaviours induced by SPS treatment were enhanced by PTEN inhibition and blocked by Akt inhibition in the ACC. Our study provides convincing evidence for the effectiveness of rTMS treatment on PTSD and suggests that its potential mechanism involves remodelling neuronal synaptic plasticity via the PTEN/Akt signalling pathway.

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Author notes

  1. Liu GH, Feng DY and Wang J contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Gaohua Liu, Zhengwu Peng, Min Cai, Ruiguo Zhang, Huaning Wang & Qingrong Tan

  2. Department of Neurobiology and Institute of Neuroscience, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Dayun Feng, Haifeng Zhang, Jing Yang & Shengxi Wu

  3. Department of Cardiac Surgery, General Hospital of Chengdu Military Region, Chengdu, 610083, People’s Republic of China

    Jian Wang

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  1. Gaohua Liu
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Contributions

Tan QR and Wu SX designed the study and wrote the protocols. Liu GH, Feng DY and Wang J completed the animal experiments and the statistical analysis. Cai M and Peng ZW participated in the behavioural tests. Zhang RG and Zhang HF participated in the morphology experiments. Yang J participated in the Western blot analysis. Wang HN managed the literature edition. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shengxi Wu or Qingrong Tan.

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Funding Sources

This work was supported by the State Key Program of the National Natural Science Foundation of China [grant number 81630032] and the National Natural Science Foundation of China [grant numbers 81371240 and 81571309].

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The authors declare that they have no conflict of interest.

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Liu, G., Feng, D., Wang, J. et al. rTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway. Mol Neurobiol 55, 3946–3958 (2018). https://doi.org/10.1007/s12035-017-0602-7

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